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thesis entitled
I. The Preparation of Ortho-, Meta- and
Parabromobenzylreaorcinola.

II. A Study of the Peroxide Catalyzed
Chlorination of the Bromotoluenea
with Sulfuryld Cfitloride.

presente 9

Richard Charles Nametz

has been accepted towards fulfillment
of the requirements for

_ll..§.._ degree in W

$4243.22”

Major professor

Date M

 

 

I. THE PREPARATION OF ORTHO-, ME'I‘A-,

AN D PARABROMBENZYLRBORCINOLS

II. A STUDY OF THE PEROXIDE CATALYZED
CHLORINATION OF THE BIDFDTOLUEN‘EB WITH

SMFU'RYL CHLORIDE

By

Richard Charles Nametz

A THESIS

Submitted to the School of Graduate Studies of Michigan
State College of Agriculture and Applied Science
in partial fulfillment of the requirements
for the degree of

MASTER OF SCIENCE
Department of Chemistry

1950

ACKNOWLEDGMENT

I wish to express my sincere appreciation
to Dr. G. L. Goerner whose guidance and

help have made this work possible.

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acetates
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239.1399

TABLE OF CONTENTS

PART I. THE PREPARATION OF ORTHO-, leTA-, AND PARABROTTOBENZYL—
RESORCINOLS

Page
INTRODUCTION..................................................... 1
EXPERIMENTAL..................................................... 4

I. Chemicals............................................... 4

II. Preparation of p-Bromobemzylresorcinol.................. 6
III. Preparation of o-Bromobenzylresorcinol.................. 10
IV. Preparation of mpBromObenzylresorcinol.................. 13

V. Derivatives............................................. 17

‘VI. Method of Determination for Bromine..................... 20
DISCUSSION....................................................... 22

WY.OCQCOO00.0.0000...OOOOOOOOOOOOO00.0.0...OOOOOOOOOOOOOOOOO 26

LITE-Am CImOOOOOOOOOOOOOOOO0.00.00...OCOOOOOOOOOOOOOOOO0.... 27

PART II. A STUDY OF THE PEROXIDE CATALYZED CHLORINATION OF THE
BROMOTOLUENES'WITH SULFURYL CHLORIDE

INTRODUCTIONOCOOOO0......C000......COOOOOOOOOOOOO...O0.0.0.000... 28

MIMMTAIIOOOOOOOOCCOO00.0.0...OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO 33

I. Chemicals............................................... 33
II. Chlorination Of p-Bromo‘boluene.......................... 33

A. Prelimmw InvestigationOIOOOOOCOOOOOOOOOOOOOO 33
1. Identification of p-Chlorotoluene......... 34
2. Identification of p-Bromotoluene.......... 35
3. Identification of p-Chlorobenzyl Chloride. 35

B. Chlorination of p-Bromotoluene in the Dark..... 37
1. Identification of p-Bromobenzyl Chloride.. 39
2. Identification of p-Bromobenzyl Bromide... 39

C. Chlorination of p-Bromotoluene in the Light..

D. Effect of Solvent on the Chlorination of
p-Bromotolueneu..........................

III. Chlorination Of O-Bromotoluene........................
A. Preliminary Investigation.....................
1. Idenfiification Of 0-Ch10r0t01ueneeeeeeeo
2. Identification of o-Bromotoluene........

3. Identification of o-Chlorobenzyl
Chloride.....OOO0.0.0.0000...0.00.0...

4. Identification of o-Bromobenzyl

Chloride..............................
5. Identification of o-Bromobenzyl Bromide.
Bo Chlorination Of O’BrOmOtOJJJODOQOQeoeeeeeeeeee
IV. Chlorination Of m-Bmmotoluone........................
A. Identification of mpChlorobenzyl Chloride....
B. Identification of mpBromobenzyl Chloride.....
. C. Identification of mpBromobenzyl Bromide......
V. Preparation of the Bromobenzyl Bromides...............
A. Preparation of p-Bromobemzyl Bromide.........
B. Preparation of o-Bromobenzyl Bromide.........
C. Preparation.of mpBromobenzyl Bromide.........

DISCUSSIONOOOOCOOOOOOOOOOIOOOOOOOOOOOOOOCI0.0.0.0....00.0.00...

MWYOOOOOCO0.0.0.0....0OOOOOOOOOOOOOOOOOOOOOOCOCOOOOOOOOOOC.

LITERATURE CREDOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO00.00.000.000.

Page
40
41
42
42
43
43
43

44
44

45
46
47
48
48
48
48
49
5O
52
56

57

PART I

THE PREPARATION OF ORTHO-, MEIA-, AND

PARABROMDBENZYLRESORCINOLS

IN TRO DUC TI ON

It is well known that resorcinol and several of its alkyl de-
rivatives, especially hexylrosorcinol, show a remarkable improvement
in germicidal action over the corresponding phenols. Ilarmann (1)
has shcvn that by the introduction of the bensyl group into the
resorcinol nucleus a capound of high germicidal activity coupled
with low toxicity could be obtained. Germicidal potency is also
known to be increased in phenols and their alkyl derivatives by the
introduction of a halogm into the nucleus. Florestano (2) has tested
twenty-eight derivatives of diphaiylmethane for antibacterial activity
against tubercle bacilli. It was found that activity seemed to be
dependent on halogen and hydroxyl group substitution in the parent
compound, and more particularly upon position.

It was felt that with the introduction of a bmmobenzyl group
into the resorcinol nucleus, a compound of high antibacterial activity
would be obtained.

The main purpose of this work was to synthesise the ortho-, meta-,
and parabromobenzylresorcinols. The method chosen for the synthesis
was the condensation of the appropriate benzyl chloride and resorcinol
in the presence of aluminum chloride. Much work has been done in
this laboratory on the aluminum chloride condensation of phenols with
alkyl halides and with alcohols.

A literature survey of the aluminum chloride condensation of
phenols and alkyl halides will not be given here as this is very ably
covered by Gyorgy (3). Only those references pertinent to this work

Will be cited.

-1-

In 1926, Klarmann (1) prepared benzylresorcinol in a 50% yield
by the aluminum chloride condensation of resorcinol and benzyl-
chloride. This reaction was carried out at 50—70° for two hours using
nitrobenzene as a solvent. Klarmann also prepared benzylresorcinol
by an application of the Hoesch (4) synthesis. In this method benzo-
nitrile and resorcinol were condensed to form the ketimine hydro-
chloride in the presence of anhydrous zinc chloride by passing dry
hydrogen chloride gas through the mixture in an ethereal solution.

The benzylresorcinol was obtained in a 30% overall yield by hydroly-
sis of the ketimine hydrochloride to the ketone and a subsequent
Clemunensen reduction.

In this laboratory benzyl alcohol was substituted for benzyl
chloride in the aluminum chloride condensation. Houk (5), following
closely the method of Klarmann, condensed benzyl alcohol and resorcinol
to obtain a 25% yield (based on the resorcinol used) of bensyl re-
sorcinol.

A few years later Klarmann and v. Wowern (6) introduced a halo-
gen substituent into the unsubstituted bmzylresorcinol. p-Chlorc-
benzyl chloride and resorcinol were condensed in the presence of
aluminum chloride to obtain a 55% yield of p-chlorobenzylresorcinol.
As in his previous work, nitrobenzene was the solvent but the tempera-
ture (50 - 70°) was maintained for four hours. By applying the Hoesch
synthesis, Klarmann was also able to obtain p-chlorobenzylresorcinol
and p-bromobenzylresorcinol in yields of 33% and 55%, respectively,

from the appropriate benzcnitrile and resorcinol.

-2-

Klarmann and v. Wowern also introduced a bromine and a chlorine
atom into the resorcinol nucleus of benzylresorcinol. ihus 5-chloro-
2,4-dibydrozydiphemrlmethane was prepared in a 51% yield by the
action of a calculated amount of sulfuryl chloride on benzylresorcinol
in ether with cooling. In the same manner 5-bromo-2,4-dihydroxydi-
phenylmethane was obtained in a 71% yield by the action of a calculated
amount of bromine on benzylresorcinol.

Thus, one of the three compounds to be prepared, namely p—brcmo-
beuzylrescrcinol, had already been synthesized, although by the Hoesch
synthesis, followed by Clemensen reduction, rather than by the

Fri edel Crafts method.

_I.

EXPERIMENTAL

Chemicals

Aluminum Chloride (anhydrous pellets) Baker's Analysed.
Benzoyl Chloride, E. K., 293.
p-Bromobenzoic Acid, E. K., 1351.

Bromobenzyl Chlorides and Bromides. Prepared as described
in Part II of this thesis.

Charcoal, Norite "A” and Darco.

Ether, Baker's Anhydrous Reagent.

Ether, Baker's U. S. P. "Solvent.”

Ligroin, b.p. 60-900, E. K., P513.

Nitrobenzene, Carrier Stevens Co. (redistilled).
Potassium Thiocyanate, C. P., Baker's.

Pyridine, E. K., P214. Refluxed for two hours over barium
oxide and distilled (b.p. 112—1140 at 740 mm.).

Resorcinol, E. K., 222. Dried at 95° for at least twelve
hours.

Silver Nitrate, Merck, Reagent.

Sodium Hydroxide (pellets), Merck, Reagent.

Sodium Peroxide, C. P. , Baker.

Toluene, Merck, Reagent.

Xylene, Merck, Reagent.

p-Brcmobenzoyl Chloride. It us necessary to prepare this
reagent by a modification of the method given by Adams and
Jenkins (7) for the preparation of p-nitrobenzoyl chloride.

In a 500 ml. round-bottomed flask were mixed 20.1 g. (0.1 mole)
of p-bromobenzoic acid, and 20.8 g. (0.1 mole) of phosphorus

pentachloride. The flask was fitted with a cork bearing a

~4-

calcium chloride drying tube and placed on a steam bath.
After a few'minutes the mixture melted, a vigorous reaction
occurred, and much hydrogen chloride was evolved. After
heating for about ten minutes, the reaction was complete
and the contents of the flask poured into a 50 ml. Claisen
flask and distilled. When all the phosphorus oxychloride
had been collected, b.p. 104-108° at 740 mm., the water
condenser was changed to an air condenser and the acid
chloride distilled. p-Bromobensoyl chloride was collected
at 220 - 225° at atmospheric pressure and solidified
quickly in.the receiver and condenser. Eighteen grams or
an 82% yield of product was obtained. This material was
not further purified, but was used directly to make the

di-p-b romob ens cat as .

-5-

II. Preparation of p-Bromobenzylresorcinol

 

For all condensations a 1-1. three-necked, standard-tapered
(24/40 - 34/45 - 24/40), round-bottomed flask was used. This was
equipped with a 250 ml. dropping funnel, an addition tube, reflux
condenser protected by a calcium chloride drying tube, thermometer,
and a mechanical stit'rer of the Hershberg (8) type. Heat was supplied
by a Glascol mantle. Since all condensations were carried out in the

same manner, only the first one is described in detail.

Condensation of p-Bromobenzyl Chloride and Resorcinol.
Reactants:
Resorcinol 70 g. (0.63 mole)
p-Bromobenzyl chloride 64.7 g. (0.31 mole)
Nitrobenzene 400 g. (334 ml.)

Anhydrous aluminum chloride 50 g. (0.37 mole)

Seventy grams (0.63 mole) of resorcinol which had previously been
dried at 95° for at least twelve hours was dissolved with stirring in
300 g. of freshly distilled nitrobensene. To this solution was quickly
added 50 g. (0.37 mole) of aluminum chloride pellets. Immediately
thereafter, a solution of 64.7 g. (0.31 mole) of p-bromobenzyl chloride
in 100 g. of nitrobenzene was added dropwise to the reaction mixture.
The addition of the halide solution required about two hours. As the
solution of p-bromobenzyl chloride in hitrobenzene was added, the temp-
erature rose slowly to 48° and then dropped to 35-40".

After the latter solution had been: added, the temperature of the

reaction mixture was raised to and maintained at 65-70° for four hours.

At the end of this time the mixture was a deep red color. The reaction
mixture was allowed to cool slightly and then poured onto cracked ice
with stirring. This mixture was allowed to stand over night and that
the water layer (upper) was siphoned off, using an aspirator. The oily
layer was washed twice with 250 ml. portions of 10% hydrochloric acid
and then with water. Each wash was siphoned off with the aspirator

and discarded. An equal volume of ether was then added to the oily
layer and the whole shaken repeatedly with 500 ml. of a 10% sodium hy-
droxide solution. Since the resulting layers were very dark, it was
difficult to mks a separation. In order to facilitate seeing the
layers in the extraction, a good source of light at a higher level than
the separatory funnel was used. The alkaline solution was drawn off
and extracted several times with ether until all the nitrobensule had
been removed. The last ether extract was colorless.

The mixture was transferred to a large beaker and acidified to
Congo paper with 1:1 Ivdrcchloric acid. Upon acidification a heavy
dark red oil was liberated. The mixture was then placed on a hot plate
and boiled for twenty-five minutes with frequent stirring. After cool-
ing, the water was decanted and the oily layer washed once with distilled
water. The heavy oil was poured into a 125 ml. Allihn flask and any
material clinging to the beaker was dis solved in ether and added to the
flask. The ether and traces of water were removed by an aspirator with
some heating of the flask being necessary to relieve the last traces of
moisture.

The crude oil was distilled through a modified Allihn flask using

a three-pronged type fraction cutter and 50 m1. Erlenmeyer flasks as

-7-

receivers. Due to the high temperature at which the distillation was
carried out, it was found necessary to wrap the column of the dis-
tilling flask with asbestos tape and to heat it with a nichrcme wire
winding. For a heating bath, Crisco was found very suitable as it
withstood temperatures of 275-2800 quite well without darkening or
smoking very badly. An oil vacuum pump was used and the pressure ob-
tained was read from a finger type manometer.

The following fractions were collected:

Fraction B.p., ° 0. (mm) Bath, ° C. Distillate (g.)
1 120-200 (2) 248-250 < l
2 200-217a (2) 250-256 26.4
3 217-219 (2) 256-271 7.3

a 1Major portion distilled at 217°

It was necessary to heat the side arm with a free flame in order
to prevent clogging. Fraction 1 solidified upon collection and was
probably mostly resorcinol. Fractions 2 and 3 distilled as light
yellow viscous oils which solidified after standing several days or
after repeated stirring. The yield of crude p-bromobenzylresorcinol
was 33.7 g. or 38.9% based on the p—bromobenzylhzhlorido used. After
recrystallizing fraction 2 from a 1:1 ligroin-xylene mixture,22 g. of
p-bromobenzylresorcinol, mp. 90 - 92°, was obtained in clusters of
needles which were slightly yellowish-green in appearance. A charcoal
(”Darco") treatment seemed to remove most of the color but the product
still retained a slight grayish cast even after repeated recrystalliza-
tion. After three recrystallizations the melting point was raised to

92.5 - 93.5° on a Fischer-Johns melting point block. Klarmann and

v. Wowern (6) reported a melting point of 96°. Anal. Calcd. for

013H BrO : Br, 28.62. Found: 28.35, 28.60.

11 2
Another condensation was carried out in the same manner using

the following quantities of reactants:

Resorcinol 70 g. (0.63 mole)
p-Bromobenzyl chloride 94.4 g. (0.46 mole)
Nitrobenzene 400 g. (534 m1.)

Anhydrous aluminum chloride 50 g. (0.37 mole)

The following fractions were collected. A mantle was used to

heat the 1' lack.

Fraction B.p., ° 0. (mm.) Distillate (g.)
1 150-200 (5) < l
2 200-227 (5) 51

The yield of crude p-bromobenzylresorcinol was 51 g., or 39.6% based
on p-bromobenzyl chloride. This material, which solidified on rubbing,
was used in determining the solvent most suitable for recrystallisa-
tion.

Condensation of p-Bromobenzyl Bromide and Resorcinol.

This condensation was carried out in the same manner as the other
condensations using the same equipmmt and the following quantities of

reactants :

Resorcinol 70 g. (0.63 mole)
p-Bromobenzyl bromide 77.5 g. (0.31 mole)
Nitrobenzene 400 g. (554 m1.)

Anhydrous aluminum chloride 50 g. (0.37 mole)

The p-bromobenzyl bromide, m.p. 61-62", was prepared by the method
described on page 48. After working up the reaction mixture in the

manner previously described, the following fractions were collected.

Fraction B. p., ° C. (m) Bath, ° C. Distillate (g.)
1 150-200 (3) 200-265 0.5
2 200-218 (3) 265-275 29.5

The yield of crude p-bromobenzylresorcinol was 29.5 g. or 34.2% based
on the p-bromobenzyl bromide. As before, this product solidified upon
rubbing. By recrystallising fraction 2 from toluene, 18.4 g. of p-
bromobenzylrescrcinol, m.p. 92.5-940, was obtained. This product was
slightly colored as in the other condensations. An additional 1.95

g. of a slightly darker product, m.p. 89.5-9l°, was obtained from the

mother liquor.

III. fiepgrat ion of o-Bromobenzylresorcinol.
Condensation of o-Brcmobensyl Chloride and Resorcinol.
The following quantities of reactants were used:
Resorcinol 88 g. (0.80 mole)
o-Bromobenzyl chloride 82 g. (0.40 mole)
Nitrobensene 520 g. (438 m1.)
Anlwdrous aluminum chloride (64.0 g. (0.48 mole)
The oebromobensyl chloride, b.p. 112-1140 at l7:mn. .nd.n%? =
1.5880, was dissolved in 130 g. of the nitrobensene and added drop-
wise to the reaction vessel over a period of an hour. The temperature

of the mixture was raised and maintained between 60-70" for four hours.

-10-

The reaction mixture was worked up in the manner described in the

previous condensations and distilled.

Fraction B.p., ° 0. (mm.) Bath, ° c. Distillate (5.)
1 74-202 (2) 195-229 0.5
2 202-212.5 (2) 229-254 56.9
5 215-215 (2) 257-265 4.5

A black tarry material which amounted to 31.1 g. was left in the dis-
tilling flask. This material, which was somewhat soluble in concen-
trated sodium hydroxide solution, was not identified. The yield of
crude o-bromobenzylresorcinol was 41.4 g. or 35.7% based on the
o-bromobenzy1\fhloride used.

Fraction 2 was redistilled using a 50 m1. Claisen flask having
the column leading to the side arm filled with glass beads and wrap-

pad with asbestos tape. The fractions collected were as follows:

Fraction B.p., ° 0. (mm.) Bath, 0 c. Distillate (g.)
1 108-191 (1) 200-254 5.4
2 191-195.5 (1) 252-267 24.5
5 195.5-196 (1) 267-275 1.9

Fraction 2 was crystallized and decolorized by rubbing under toluene
to obtain 16.2 g. of o—bromobenzyl-resorcinol, m.p. 103.5-107". By
evaporating the mother liquor, 2.3 g. of product, m.p. 96-100°, was
obtained. It was found that the melting point of the product of
m.p. 103.5~107° could be raised to 109,5-1110 by one recrystallisa-
tion from toluene. However, repeated recrystallization from various

solvents (carbon tetrachloride, water) did not raise the melting point

-11..

above 112°. These values do not agree too closely with the melting
point of the product obtained in the condensation of o-bromobemzyl
bromide and resorcinol, 112-114.5° (page 13). However, no depres-
sion was shown in the melting point of the dibensoates prepared from
both products. Evidmtly the product obtained by condensing o-bromo-
benzyl chloride and resorcinol must have been slightly contaminated,
and this impurity is difficult to remove.
Another condensation was carried out in the same manner using

the following quantities of reactants:

Resorcinol 70 g. (0.63 mole)

o-Bromobenzyl chloride 63.7 g. (0.31 mole)

Nitrobenzene 400 g. (554 m1.)

Anlvdrous aluminum chloride 50 g. (0.37 mole)

The following fractions were collected:

Fraction B.p., ° 0. (mm.) Bath, ° 0. Distillate (g.)
1 140-195 (5) to 256 2.4
2 195-216 (5) 256-240 8.4
5 216-228 (5) 240-265 16.0

The yield of crude o-bromobenzylresorcinol obtained was 28.4 g. or

30.4% based on the o-bromobensyl chloride used.

Condensation of o-Bromobenzyl Bromide and Resorcinol.
Reactants:
Resorcinol 70 g. (0.63 mole)

o-Bromobenzyl bromide 77.5 g. (0.31 mole)

Nitrobenzene 400 g. (334 m1.)

Anhydrous aluminum chloride 50 g. (0.37 mole)

The equipment and method used for this condmsation were the same as
in previous condensations. The o-bromobenzyl bromide, b.p. 129-130°
at 16.5 mm., was prepared as described on page 49. The following

fractions were obtained:

Fraction B. p., 0 c. (nmn) Bath, ° 0. Distillate (g.)
1 155-211 (5) to 252 ( 1.0
2 211-212 (5) 232-246 25.9

The yield of crude o-bromobenzylresorcinol was 23.9 g. or 27.5% of
theory based on the o-bromobenzyl bromide. By dissolving this material
in a large volume of boiling water and decanting away from the dark
insoluble oils, 10 g. of o-bromobenzylresorcinol, m.p. 112.5-1140, was
obtained. This compound crystallised as fine, slightly colored needles
from water. A small portion of this was again recrystallized from
water to obtain fine white needles, m.p. ll3.5-ll4.2°. This material
was analyzed after drying in a vacuum desiccator. Anal. Calcd. for

0135116102: 6,. 26.62. Found: 13,-, 26.67, 26.72.

IV. Preparation of m-Bromobanzylresorcinol.
Condensation of m-Bromobenzyl Chloride and Resorcinol.
This condensation was carried out in the manner described pre-
viously using the following quantities of reactants:
Resorcinol 70 g. (0.63 mole)

m-Bromobenzyl chloride 64.7 g. (0.31 mole)

-13-

Nitrobenzene 400 g. (334 ml.)

Anhydrous aluminum chloride 50 g. (0.57 mole)

The m—bromobenzyl chloride, b.p. 116-118.5° at 17 mm., was obtained
from the distillation described on page 47. This condensation pro-
ceeded essentially the same as all the others, except that a dark
semicrystalline solid was isolated after acidification of the alkaline
attract, boiling, and chilling the mixture in an ice bath. This solid

was filtered, transferred to the distilling flask, and distilled as

before.
Fraction B.p., ° 0. (mm.) Bath, 0 c. Distillate (5.)
1 65-205 (2.5) to 225 0.5
2 205-209 (2) 225-247 5.5
5 209-215 (2) 247-261 26.5

The tarry naterial left in the flask amounted to 16.5 g. and was not
identified. The yield of crude m-bromobenzylresorcinol, isolated as
a light yellow viscous oil, was 31.6 g. or » 36.4% based on the m-brome-
benzyl chloride used. After repeated rubbing fraction 5 solidified.
Recrystallization from toluene gave 21.? g. of light yellow plates,
m.p. 59.5-63.50. Upon decolorizing a small portion of this material
wdth Norite ”AP in.toluene, white, glistening plates were obtained.
These melted from 59-66.5°.

Believing that perhaps the m-bromobenzyl chloride used had been
contaminated with a small amount of m-chlorobenzyl bromide, and that
the condensation had yielded a mixture difficult to separate, the

dibenzoate of this material was prepared by the method described on

-l4-

*

page 17 and purified. The melting point of the dibenzoate was 95.5-960.
This dibensoate was hydrolyzed as follows, using a modification of the
procedure described by Shriner and Fuson (9).

Twenty-five milliliters of diethylene glycol, 8 ml. of water, and
4.8 g. of solid potassium hydroxide were placed in a 50 m1. round-
bottomed flall: and a boiling chip added. This mixture was shaken until
most of the potassium hydroxide had dissolved. Three grams of the
dibenzoate of m-bromobenzylresoroinol was added, a reflux condenser
placed in position, and the mixture refluxed for one hour. Almost im-
mediately the solution became deep red in color. The solution was
cooled and acidified with dilute sulfuric acid. A white, finely divided
precipitate was thrown down. The mixture was extracted with ether and
the ether extract washed with water. In order to remove the benzoio
acid formed, the ether layer was extracted twice with sodium bicarbonate
solution and finally with water. Upon evaporation of the other solution,
a light red viscous oil was obtained. Glisteming plates, m.p. 59-66°,
were obtained by dissolving this oil in hot toluene and cooling.

A second condensation was carried out in the same manner, using
the same reactants in the same quantities. The following fractions

were collected in the distillation:

Fraction B.p.,o 0. (mm.) Bath,° c. Distillate (5.)
1 125-190 (2) 220-240 1
2 190-225a (2) 240-254 6.6
, 5 225-229 (2) 254-270 12.4

a Major portion distilled at 222-225°_

-15..

The yield of crude m-bromobenzylresorcinol was 19.0 g. or 21.9% based

on m-bromobenzyl chloride.

Condensation of m-Bromobenzyl Bromide and Resorcinol.

It was believed that a product having a better melting point might
be isolated by carrying out this condensation. The following quantities
of reactants were used:

Resorcinol 110 g. (1.01 moles)

m-Bromobenzyl bromide 125 g. (0.50 mole)

Nitrobenzene 575 g. (460 ml.)

Anhydrous aluminum chloride 80 g. (0.6 mole)
The m-bromobenzyl bromide, b.p. 125--126o at 12 mm., was prepared by
the procedure described on page 50. The m-bromobenzyl bromide was
dissolved in 165 g. of the nitrobenzene and added dropwise to the re-
action mixture over a period of two hours. The rest of the reaction
was carried out as described above. Upon distillation of the semi-
crystalline solid, 8.4 g. of light red oil was collected, boiling at
ISO-210° at 1 mm. Considering this as crude m-bromobenzylresorcinol,
a yield of 10.3% was obtained based on m-bromobensyl bromide. A small
portion of this crude distillate was recrystallized from toluene and
decolorized with Norite "A" to give slightly colored, glistening
plates, m.p. 59-640.

A small amount of the recrystallised m-bromobensylresorcinol from
the first condensation was placed in a vacuum desiccator over mineral
oil for several days. This material exhibited the following melting

point: Some of the crystals melted at 60-64°. The crystals that were

-15-

left were clearly defined and did not melt until 75° and then melted

at 75-77°. After melting some of the compound in an oven at 125° for
ten minutes and cooling the product until crystallization was complete,
a melting point of 59-60.5° and 77-79° was again obtained. It is pos-
sible that two polymorphic forms of this compound exist. The material
which had been dried over mineral oil was analyzed and gave the follow-
ing bromine value. Anal. Calcd. for 01311118102: Br, 28.62. Found:

Br, 28.41, 28.54.

V. Derivatives

 

Attempts were made to prepare five different types of derivatives
of the bromobenzylresorcinols. These were the dibmzoates, the di-p-
bromobenzoates, the diacetates, the diaryloxyaoetic acids, and the
p—tosyl derivatives. Of these only the dibenzoates and di-p-bromobens-
oates were satisfactory. The diacetates, prepared by the method of
Chattaway (10), were apparently oils. The p-tosyl derivative of
m-bromobenzylresorcinol failed to crystallize, while the diaryloxyacetic
acid of m-bromobensylresorcinol was obtained in a yield too snll for
halogen determination. The product obtained upon reacting m-bromo-
benzylresorcinol and chloroacetic acid according to the method of

Koelsch (11) melted at 172-174.5°.

Dib en: oat es

The dibenzoates were prepared using essentially the method given

by Gyorgy (3).
The following mterials were placed in a dry 10-inch pyrex test

-17-

tube: 1.5 g. of the bromobenxylresorcinol, 5 m1. of dry pyridine,

and 2 ml. of benzoyl chloride. As soon as the acid chloride was added,
the tube became quite warm, the mixture solidified and turned light
brown in color. The reaction mixture was protected by a calcium chloride
tube and placed on a steam bath for an hour. At the and of this time
the contents had darkened somewhat.

After allowing the mixture to cool, 10 ml. of water wad added to
the tube. The mixture was transferred to a separatory funnel, 20 - 30
ml. of ether added and the whole shaken . The water layer was drawn
off and the other layer washed twice with a 6 N sulfuric acid solution,
a 10% sodium carbonate solution, and then with water.

After evaporating the other from the solution a light tan oil was
left. Only the dibenzoate of m-bromobenzylresorcinol could be made to
crystallize on rubbing. The dibenzoates of the ortho- and para-bronc-
benzylresorcinols were found to crystallize from 95% ethanol as granu-
lar crystals. The dibenzoate of the meta isomer was recrystallized
from 95% ethanol in the form of shiny plates. In all cases the yields

were excellent and purification quite easy.

Di-p-bromobenzoates

The di-p-bromobensoates were prepared essentially the same as the
dibenzoates, except that 2.4 g. of p-bromobenzoyl chloride, prepared
by the method given on page 4, 1.5 g. of the bromobenzylresorcinol
and 6.5 ml. of pyridine were used. The mixture was heated for a period
of two hours on the steam bath and then worked up. The di-p-bromobenz-

oates were all found to be only slightly soluble in absolute ethanol

 

 

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-19..

and much solvent had to be used to recrystallise them. The di-p-
bromobenzoates crystallized as granular crystals. In all cases, the

yields were only fair.

VI. Method of Determination for Bromine

 

The method used for the determination of bromine was that given
by Lamp and Broderson (12). This method involves a fusion of the
organic compound with sodium peroxide in a Parr bomb in the presence
of potassium nitrate and cane sugar. The fusion was then followed
by a Volhard determination for halogen.

Approximately 1.5 g. of finely ground potassium nitrate, 0.4 to
0.45 g. of cane sugar, and 0.2 to 0.25 g. (accurately weighbd) of the
compound to be analysed was placed in the fusion cup of the bomb.
About 10 g. of sodium peroxide was then added quickly and the bomb
sealed. After shaking the bomb thoroughly for about five minutes,
the cup was tapped lightly on the desk to get materials to the bottom
and ignited in the hottest part of a Bunsen flame until fusion had
taken place (one to three minutes).

The bomb was then cooled immediately under the water tap, opened,
the cup and top rinsed with distilled water, and placed in a 600 m1.
beaker. The beaker was covered with a watch glass and enough hot
water added to cover the fusion cup. After the evolution of gases had
ceased the solution was digested for several minutes and the cup and
top rinsed and removed. An excess of standard 0.11! silver nitrate solu-

tion was added and the mixture boiled gently for fifteen minutes.

-20-

The mixture was cooled, acidified with concentrated nitric acid,
and hydrazine sulfate added in small portions until frothing had
ceased. The determination was completed by a titration of the excess
silver nitrate with standard potassium thiocyanate in the presence of
ferric ion (3-5 ml. of ferric alum solution for each 200 ml. of solu-
tion). The addition of 5 ml. of nitrobenzene facilitated seeing the
endpoint by surrounding the silver bromide and holding it on the

bottom of the beaker.

DISCUSSION

During the course of this work, the three isomeric bromobenzyl-
resorcinols have been prepared from resorcinol, the appropriate bromo-
benzyl chloride or bromide and anhydrous aluminum chloride, using nitro-
benzene as the solvent. Of the above compounds, only p-bromobenzyl-
resorcinol has been reported previously (6). The yields and melting
points of these bromobenzyl-resorcinols are given in Table II. In all
cases the yield from the bromobenzyl chloride was higher than from the
corresponding bromide.

From Table II it may be obsewed that the melting point of the
bromobenzylresorcinol increases in the order meta<para<ortho. The
o-bromobemzylresorcinol prepared from o-bromobenzyl bromide melted at
a slightly higher temperature than that prepared from the o-bromobenzyl
chloride. All attempts to raise the melting point of the compound
prepared from the chloride were futile. These attempts included recrys-
tallization from water, toluene, and carbon tetrachloride, then redis-
tillation followed by recrystallization from the above solvents.
m-Bromobenzylresorcinol appeared to be rather impure from the melting
point of 59-66.5°. However, after being melted completely and them per-
mitted to cool and solidify, the melting point was observed to be
59-60.5° for some czystals and 77-790 for the rest of the crystals. This
peculiarity in melting point may be due to polymorphism. p—Bromobenzyl-
resorcinol was prepared in a 39.2% average yield from p-bromobenzyl
chloride by the Friedel-Crafts method. Klarmann and v. Wowem (6) re-

ported that a 55% yield of this compound was obtained from

 

 

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e.e»
eenh.~e m.en m.neum.~e e.en “endogeeeeflseeeheaesmua
e sense «.0»
eeueh m.oH use m.oe-eh e.H~ V Heqneheeeinaeeehesehmia
«.0»
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-23-

p-bromobenzonitrile and resorcinol via the Hoesch synthesis and a
Clemensen reduction of the ketone obtained. Their compound was re-
ported to melt at 96° whereas the highest melting point obtained in
the present work was 92.5-940.

No systemtic study for determining the optimm quantities of re-
actants was made, the quantities being similar to those used by
Klarmann and v. Wowern (6) in the preparation of p-chlorobenzylresor-
cinol by the Friedel-Crafts method. However, it was observed that in-

’ creasing the amount of p-bromobenzyl chloride from 0.31 to 0.46 mole,
while holding the resorcinol constant at 0.63 mole, did not materially
increase the yield of the desired product. On the other hand, in the
preparation of o-bromobenzylresorcinol, it was found that by increasing
the o-bromobenzyl chloride from 0.31 to 0.40 mole and the other re-
actants proportionately, the yield was increased from 30.4% to 35.7%.

In general the bromobenzylresorcinols are solids. They distil,
usually with superheating, at 200 to 220° at 2 mm. as light yellow oils
which crystallize slowly. They are so easily soluble in solvents con-
taining oxygen, such as alcohols and esters, that they camot be recover-
ed from then. They are very insoluble in aliphatic hydrocarbons such as
petroleum ether, hexane, heptane, etc. They can be crystallised with
difficulty from toluene, xylene-ligroin, carbon tetrachloride, and large
volumes of water. Although the pure solids are relatively stable, the
solutions-appear to be easily aidised. It is very difficult to remove

traces of color from them.

The structure of the bromObenzylresorcinols

OH

is assumed to be that shown. This is in agreement with structure as-
signed by Klarmann (l, 6) to benzylated resorcinols, with the structure
of hexylresorcinol, and with the fact that substitution in resorcinol
is ortho to one hydroxyl group and para to the other, or'in the 4 posi-
tion.

The antibacterial action.of the'bromobensylresorcinols is being

investigated.

-25-

WY

The preparation of ortho-, meta-, and parabromobenzylresorcinols
by the Friedel-Crafts method has been described. Of these, the ortho
and meta isomers are reported for the first time.

The di-benzoates and di-p-bromobenzoates lave been prepared as

derivatives .

LITERATURE CITED

1. E. Klarmann, J. Am. Chem. Soc., 42, 791 (1926).

2. H. J. Florestano, J. Pharmacol. Exp. Therap., _9_§, 238 (1949).

3. H. Gyorgy, Ph. D. Thesis, Michigan State College, 1950.

4. K. Hoesch, Ber., 35, 1122 (1915).

5. A. L. Houk, Bachelor's Thesis, Michigan State College, 1926.

6. E. Klarmann and J. v.'waern, J. Am. Chem. Soc., E1, 605 (1929).

'I. R. Adams and R. L. Jenkins in “Organic Syntheses,a Coll. Vol. I,
and. Ede, JOhn Wiley and Sons, Ince' New York, No Yo. 1944,
p. 394.

Be Be Be Hershberg, Inde mge Chane, Ana-10 Ede, E, 313 (1936)e

9. R. L. Shriner and R. C. Fuson, "The Systematic Identification of
Organic Compounds," 3rd Ed., John Wiley and Sons, Inc.,
New York. N. Ye, 1948. P. 133.

10. F. D. Chattaway, J. Chem. Soc., 2495 (1931).

11. C. F. Koelsch, J. Am. Chem. Soc., 53, 304 (1931).

12. J. F. Lamp and H. J. Broderson, J. Am. Chem. Soc., 39, 2069 (1917).

-27-

PART II

A STUDY OF THE PERQXIDE CATALYZED
CHLORINATION OF THE BROMDTOLUENES

'WITH SULFURYL CHLORIDE

INTRODUCTION

In 1939, Kharasch and Brown (1) described a method for the side
chain chlorination of aromatic hydrocarbons. The method consisted
essentially of heating together the hydrocarbon and sulfuryl chloride
in the presence of catalytic amounts of benzoyl peroxide (other
peroxides were employed but benzoyl peroxide was found to be the most
suitable).

Thus toluene, p-chlorotoluene, ethyl benzene, isopropylbenzene and
mpxylene'wore readily chlorinated in good yields by sulfuryl chloride.
In some cases carbon tetrachloride, methylene chloride, and benzene
were used as inert solvents. The purpose of the solvent was to decrease
the vigor of the reaction by dilution.and also to keep oxygen, which
is an inhibitor, away from the reaction mixture. Kharasch and Brown
proposed the following mechanism.for side chain chlorination, where
06H5-, Re, C1-, etc., represent free radicals. It involves the de-
composition of the benzoyl peroxide at the reaction temperature initiat-

ing a chain reaction.

063500-0-0-000635 -———————~ 20635- + 2002 (1)
c6H5- + 302012 -——————e- -sozc1 + C6H501 (2)
40201 _. so2 + Cl- (3)
01- + RH -—~ R- mm (4)
R- + 302c12 -—-——-—~. R01 e -sozc1 (5)
Cl- 1. RH ——e- RCl {- H- (6)
H- + 302012 -——-———e- H01 + -80201 (7)

These authors considered equations (6) and (7) as being very

unlikely. The chain could be broken by the following steps.

R- + R- —» R-R (e)
R- 4- 01- ——-e- R-Cl,etc. (9)
H- 4- H- ——e- H2 . (10)
H- 1- Cl- ——e- HCl , etc. (11)

In addition, impurities could break the chain reaction by combining
with the atoms or free radicals. A

In this laboratory, Gyorgy (2) first employed this method for
the chlorination of the bromotoluenes. In all runs three moles of
the bromotoluene, one mole of sulfuryl chloride, and 0.002 mole of
benzoyl peroxide were used. This ratio was used supposedly to keep
dichlorimtion of the side chain at a minimum and to reduce the vigor
of the reaction by dilution. The reaction mixture was heated slowly
to 93° - 97° C. (depending on the bromotoluene) in a round-bottomed
flask equipped with an efficient condenser. As the initiation tempera-
ture was approached, the reaction mixture underwent a color change
from a light yellow to a reddish orange. Whal the initiation tempera-
ture was reached a vigorous reaction occurred as evidenced by a rapid
evolution of gases and the appearance of some liquid in the condenser.
The liquid was noted to be deep red in color, but this color rapidly
disappeared. At the end of about thirty minutes, the reaction was
complete and the mixture was heated to gentle reflux for a short time.
Any remaining gases were sucked off by means of an aspirator and the

mixture distilled.

The reaction mixture from the chlorination of p-bromotoluene was
distilled from a normal Claism flask, and those from the ortho and
meta bromotoluenes through a 6" heated column. The average yields of
the bromobenzyl chlorides after rectification were reported as 78% for
the para, 63% for the ortho, and 57% for the meta isomer. Gyorgy men-
tionsdthat low boiling fractions and high boiling fractions were obtain-
ed in all cases, but these fractions were not identified.

hiring the course of the preparation of p-bromobenzylresorcinol,
it became necessary to prepare p-bromobenzyl chloride as an intermediate.
After several attempts to synthesize the intermediate in good yields
by the method mentioned above, it became apparent that side reactions
were also taking place. Several of the low boiling fractions were care-
fully investigated and p-chlorotoluene was isolated and identified.

It seemed desirable, after noting nuclear bromine displacenent in
this reaction, to further investigate the products formed in the sulfuryl
chloride chlorination of the bromotoluenes.

Replacement of bromine by chlorine in chlorinations involving
gaseous chlorine and aromatic bromides has frequmitly been observed.

Eibner (3) showed that chlorine could replace bromine from bromo-
benzene completely so that mono-chlorobenzene was obtained in addition
to sill quantities of other substances.

Srpek (4), in the chlorination of p-bromotoluene to form the bensyl-
chloride, obtained p-bromobenzyl bromide as one of the products.

Boeseken (5), Jacobs and Heidelberger (6), and Berger (7) all obtained
products in the chlorination of para, ortho, and meta bromotoluenes.

respectively, that had an increased bromine content in the side chain.

-30..

.Also Olivier (8), hoping to prepare 3,5-dibromobenzyl chloride
by the chlorination of 3,5-dibromotoluene at high temperature, always
obtained a mixture of products that he could neither separate nor
identify.

Asinger (9), hoping to prepare 3¥bromo-5-chlorobenzaldehyds from
3-bromo-5-chlorotoluene by chlorination to the corresponding bensal
chloride and subsequent hydrolysis to the benzaldehyde obtained 3,5-di-
chlorobenzaldehyde as a final product. A closer investigation showed
that the nuclear bromine did not escape along with the hydrogen chloride
given off but entered the side chain.

Asinger made a study of the side chain chlorination of ortho, meta,
and para bromotoluenes and also 3,5-dibromotoluene. He found that
partial or complete replacement of the nuclear bromine could occur and
that the products formed were mixtures from which the benzyl or benzal
chloride could not be isolated in.pure form. .Also the nuclear bromine,
after‘being replaced, entered the side chain. Chlorination to the
benzyl chlorides and benzal chlorides was carried out at 1800 - 200° C.
(in some cases at 160° - 170°). Replacement of nuclear'bromine was
shown to occur less at lower temperatures than.at higher temperatures.
Total halogen and side chain halogen'were determined after the theoreti-
cal amount of chlorine had been taken up. For example, in the chlorina-
tion of p-bromotoluene to form.the'benzyl chloride, the following
analysis of the reaction.mixture was obtained after it had been freed

of hydrogen halide gases hy placing it over alkali.

-31-

Total chlorine-bromine value

 

Calculated on C7HGClBr

Calc. Cl 17.26% Br 38.91%
Found C1 17.58% Br 38.45%

One would assume that pure p-bromobenzyl chloride had been formed.
However, upon side chain halogen determination, Asinger showed this was
not the case.

Bide chain halogen

 

Calc. Cl 17.26% Br 0.00%

Found Cl 6.78% Br 14.12%
After recrystallizing the mixture twice from ethanol, 0. product was ob-
tained that melted at 43° - 44° C. and gave the following chlorine-
bromine value.

Total chlorine-bromine value

Calculated on C7H6C1Br

Cale. C1 17.26% Br 38.91%

Found 01 14.64% Br 42.87%

Side chain hglggen

Gale. (:1 17.26% Br 0.00%

Found Cl 6.92% Br 22.48%

-32..

EXPERIMEH‘JTAL

1. Chemicals
Bromine, N. F. 7., Dow.
o-Bromotoluenne, Dow (redistilled).
m-Bromotoluene, E. K. 1142 (redistilled).
p—Bromotoluene, Dow (redistilled).
o-Chlorobenzoic Acid, E. K. 552.
p-Chlorobenzoic Acid, E. K. 627.
Ethyl dlcohol, 95% and Absolute, Commercial Solvents.
Ether, Baker's Anhydrous Reagent.
Ether, Baker's U. S. P. "Solvent.”

Magnesium Metal Turnings (for Grignard's reaction),
Baker's Analyzed.

Picric Acid, C. P. Baker.

Potassium Permnganate, C. P. Baker.
Sodium Hydroxide (pellets), Merck, Reagent.
Sulfuryl Chloride, E. K., P322.

Thiourea, E. K., P497.

II. Chlorination of p-Bromotoluene

 

A. Preliminary Investigation.

For a preliminary investigation of the products formed in this
reaction, the low boiling fractions of several runs were obtained from
Gyorgy and vacuum distilled. For the distillation, a Fenske type

column, 51 cm. long and packed with 1/16 in. I. D. case hardened glass

-33-

helices was used. The take-off was of the cold finger type arranged
so that small fractions could be taken under vacuum.

The following definite fractions were obtained in the distillation.

Fraction Identified as B.p. , °c. (mm.) 11D
1 p-Chlorotoluenea 47-43 ( 12) 1.5209b
2 p-Bromotoluenec 63-65 (12 ) -........
3 P-ChlorobensylC1 94. 5-95 . 5 (12 ) ....--
chloride

a. Large fraction. b. At 20.20. c. Large fraction which solid-
ified upon collection. d. A cull fraction that solidified upon
standing.

1. Identification of p-Chlorotoluene.

Since the boiling point and refractive index of fraction I agreed
closely with the values given by Huntress (10) for p-chlorotoluene
(b.p. 45.6-480/12 mm., and n%0 g 1.521), there was good reason to be-
lieve that p-chlorotoluene had been formed in the chlorination.

An alkaline permanganate oxidation of fraction 1 was carried out
using the procedure of Cheronis and Entriken (11).

In a 50 m1. roundAbottomed flask equipped with a reflux condenser
were placed 1.5 g. of solid potassium permanganate, 25 m1. of water,
0.5 m1. of 6 N sodium hydroxide, and a boiling chip. Five hundred
milligrams of fraction 1 was added and the mixture refluxed for an hour
and three quarters. At the end of this time, the permanganate color
had almost disappeared, and the characteristic brown precipitate of

manganese dioxide was present.

-34-

After the reaction mixture cooled, it was acidified to Congo red
paper with dilute sulfuric acid. Sodium bisulfite was then added in
small quantities to the mixture until the solution cleared. The solu-
tion was boiled for a few minutes, filtered, and cooled. Upon cooling,
the oxidation product crystallized in white needles which were filtered
and recrystallized from 10 ml. of hot alcohol. Water was then added
drop-wise to the filtered, hot alcoholic solution until a slight turbid-
ity resulted. The solution was cooled and the product filtered and
dried at room temperature.

The melting point of the product (taken in a sealed capillary) was
235-236.5°. When admixed with an authentic sample of p-chlorobenzoic

acid, m.p. 235-236°, it melted at 233.5-235°.

2. Identification of p—Bromotoluene.

Unreacted p-bromotoluene, fraction 2, constituted a very large frac-
tion and solidified on collection in the receiver. The boiling point
checked closely with that given by distillation of the known p-brcmo-
toluene. This material was noted to melt on a warm day in the laboratory
when the temperature was over 28°. Bigelew (12) lists a melting point
of 25-26°. Gyorgy (13) reported a boiling point of 70-74° at 12 m.,
but mmtioned that he could never get the recovered p-bromotoluene to

8011d1fye

‘ 3. Identification of p-Chlorobenzyl Chloride.
me to the fact that p-chlcrotoluene had been identified as one of
the products in the chlorination reaction, and the boiling point of

fraction 3 agreed closely with that given by Huntress (14) for

-35..

p-chlorobenzyl chloride (94-96° at 14 mm.), there was good reason to
believe this fraction to be p-chlorobenzyl chloride. Fraction 3 (b.p.
94.5-95.5° at 12 mm.) was characterized by conversion to the Grignard
reagent, carbonation, and subsequent hydrolysis to the phenylacetic
acid. The procedure was essentially the same as that given by Cheronis
and Entrilcen (15) for the preparation of phenylacetic acid.

Two hundred and forty milligrams of magnesium turnings was placed
in a 10 in. pyrex test tube that had bem dried by heating with a flame.
A solution of 1.4 g. of fraction 3 in 8 m1. of anhydrous ether was
added all at once to the magnesium. The reaction started very easily
after crushing a few magnesium turnings with the end of a stirring red.
A cork bearing a finger condenser and a soda-lime tube was placed
tightly in the mouth of the tube. After about 17"th minutes, the re-
action ceased and the solution as refluxed for a short period and
allowed to cool. The reagent was a dark green color.

The carbonation of the Grignard reagent was effected by dropping
small pieces of dry ice into the tube after each piece had been wiped
with a dry cloth. A vigorous reaction occurred and most of the ether
was lost. After the reaction had ceased, the mixture was stirred, 10
m1. of ether added, and the addition product decomposed with a mixture
of 8 g. of ice and 4 ml. of concentrated sulfuric acid. The resulting
mixture was filtered from the unreacted mgnesium into a 250 m1.
separatory funnel, The ether layer was separated, the water layer ex-
tracted once with ether, and the ether extracts combined.

The water layer was tested for bromide ion in the following manner.

One milliliter of the solution and 1 m1. of chloroform were placed in

-36-

a small test tube and two drops of chlorine water added. After several
minutes the organic layer became light brown in color. This would inp
dicate that fraction 3 was probably slightly contaminated with a bromide.

In order to isolate the acid, the other solution was extracted
once with a 5% sodium.hydroxide solution, once with.water and the ex-
tracts combined.

Upon careful acidification of these extracts with dilute hydro-
chloric acid, follownd by cooling, the acid crystallized as fine, white
needles which were filtered and dried at room temperature. .After re-
crystallization from.dilute alcohol, the compound melted at 101.5-
103.5°.

'When admixed with p-chlorophenylacetic acid, prepared in'the same
manner as above from.p-chlorobenzyl chloride and melting at 103-105°,

it melted at 102-105°.

B. Chlorination of p-Bromotoluene in the Dark.

The following reaction.was carried out using only an 8 candle
power red safety light for illumination. Due to the large amount of
gases given off, it was necessary to carry out the chlorination in the
hood.

In a 3-1. one-necked, round-bottomed flask equipped with a ground
glass bulb condenser, a thermometer extending through.the condenser to
the bottom.of the flask, and heated by a Glascol mantle'were placed
514 g. (3 moles) of pébromotoluene, 135 g. (1 mole) sulfuryl chloride,
and 0.5 g. of benzqyl peroxide. The p-bromotoluene used was redistilled

(b.p. 82° at 27 mm.) from a Claisen flask, and the sulfuryl chloride

was distilled through a 30 cm. Fenske column immediately before use
(b.p. 67° at 739.6 mm.). The reactants'were heated slowly to 100°.

At this temperature the reaction commenced. The mantle was removed
and the reaction flask cooled with an ice bath. Even with external
cooling the reaction proceeded'violently, being accompanied by the
evolution of gases and vigorous reflux in the condenser. At 40°, the
reaction still proceeded but not as vigorously as before. After about
thirty minutes, spontaneous reaction had ceased and the mixture was
heated to 110° for a short time.

The reaction mixture was transferred to a 500 ml. two-necked, round-
bottomed flask equipped with a thermometer well and capillary tube, the
corrosive vapors pulled off by the water aspirator and the material
distilled through.the Fenske column previously described (page 33). The
pressure was reduced by means of an oil vacuum.pump. The following frac-

tions were obtained: .

Fraction Identified as B.p., ° C. (mm.) Distil- No. of
late (g.) moles
l p-Chlorotoluene 47.5-50 (12) 27.9 0.22
2 50 -62 (12) 8.5
3 p-Bromotoluenea 62 -64.5 (12) 317.4 1.85
4 75 -92 (12) 2.1
5 92 -94 (12) .83
6 p-Chlorobenzyl _
chlorideb 94 -97 (12) 2.55 0.02
7 ° 97 -100 (12) 1.66
8 p-Bromobenzyl
chlorided 100 -115 (12) 77.2 0.38
9 p-Bromobenzyl
bromidee 115 -124 (11) 46.2 0.18

a,b,c,d,e. These fractions solidified upon collection.
Fraction 1, identified as p-chlerotoluene in the preliminary in»

vestigation (page 34), amounted to 0.22 mole of p-chlorotoluene produced.

-38..

Fraction 2 can be considered as a mixture of p-chlorotoluene and
p-b romotoluene.

Fraction 3, p-bromotoluene, solidified upon collection in the re-
ceiver and amounted to 1.8 moles.

The fractions intermediate between those of p-bromotoluene and p-
chlorobenzyl chloride, fractions 4 and 5, were considered as mixtures
of p-bromotoluene and p-chlorobenzyl chloride.

Fraction 6, which amounted to 2.55 g., was considered as p-chlorc-
benzyl chloride. This fraction was collected at approximately the same

boiling point as that identified as p-chlorobenzyl chloride on page 35 .

1. Identification of p-Bromobenzyl Chloride.

Upon recrystallizing fraction 8 from 95% alcohol, 71.8 g. of long
needles was obtained, m. p. 40-41° on a Fischer-Johns melting point
block. Some of the literature values for p-bromobenzyl chloride are as
follows: 38-39° (16), 40° (17), 41° (5), 4o-42° (19). The total yield
of recrystallized p-brcmobenzyl chloride was 34.9%, based on the sul-

furyl chloride us ed.

2. Identification of p-Bromobenzyl Bromide.

By recrystallizing fraction 9 from 95% alcohol, 40.9 g. of a product
crystallizing in long needles was obtained. This material gave a melt-
ing point of 60-62°. This value agrees closely with that found by the
bromination of p-bromotoluene, m.p. 61--62o (page 48).

The material obtained by recrystallizing fraction 9 was identified

as p-bromobenzyl bromide by a mixed melting point with a sample of

-3 9..

known p-bronmbenzyl bromide, prepared as on page 48, and by analysis.
This material when admixed with known p-bromobenzyl bromide, m.p.
61-62°, melted at 60.5-62.5°.

Analysis of this material after drying in a vacuum desiccator
gave the following bromine value. Anal. Calcd. for C7H6Br2: Br, 63.96.

‘Found: Br, 63.78 and 64.01.

C. Chlorination of p-Bromotoluene in the Light.

Another chlorination was carried out in daylight using the same
equipment and the same quantities of reactants as described on page 57.

This time the reaction mixture was noted to undergo a character-
istic color change from light yellow to deep orange as it was slowly
heated to 93°. At this temperature the reaction commenced, the mantle
was removed, and the reaction flask was cooled with anice bath. Even
with external cooling the evolution of gases was very vigorous and much
red liquid flooded the condenser.

After the reaction had ceased (about twenty minutes), the mntle
was again adjusted and the mixture heated to 110° for a short time.
Upon working up the reaction mixture in the previously described mn-

ner, the same products were recovered as before in the yields indicated.

Fraction Identified as B.p., °c. (mm.) Distil- No. of
late ( g. ) moles
1 p-Chlorotoluene 53-55 (16) 35 . 6 0.28
2 -- 61-63 (16) 1.7 --
3 p-Bromotoluene 70-74 ( 18) 327. 6 l. 91
4 , a. 87-102 (16) 2.0 --
5 p-Bromob enzyl
chloride 107-120 (12) 96.0b 0.47
6 p-Bromob enzyl
bromide 120-130 (12) 26.6b 0.11

-40—

a. This was probably a mixture of p-bromotoluene and p—chloro-
benzyl chloride. The amount of material boiling at the
temperature and pressure given for p—chlorobenzyl chloride
was very small.

b. Yield of unrecrystallized product.

D. Effects of a Solvent on the Chlorination of p-Bromotoluene.

To determine the effect of a solvent on the chlorination, carbon
tetrachloride was used. The reaction was carried out as in the previous
cases, using the following quantities of reactants:

p-Bromotoluene -- 342 g. (2 moles)
Sulfuryl chloride -- 135 g. (1 mole)

Carbon tetrachloride -- 100 ml. (approx. 1 mole)
Benzoyl peroxide -- 0.5 g. (0.00203 mole)

The reactants were placed in a 2 1. three-necked flask equipped
with two ground glass bulb condensers and thermometer. At 75° some
refluxing occurred. As the temperature was raised, the same color change
from light yellow to deep orange took place, and the refluxing increased.
At 93° the vigorous reaction again occurred, much red liquid flooded the
condenser, and no diminution in the violence of the reaction was ob—
served. The flask was cooled with an ice bath for a short time, the ice
bath removed, and the reaction allowed to proceed by itself. The liquid
was still bubbling after five hours.

The reaction mixture was worked up in the manner previously des-
cribed, the solvent removed at atmospheric pressure and the material
boiling below 105° at 12 mm. distilled from a Claisen flask. This ma-
terial no redistilled through a Fenske column and the following

quantities of products were obtained:

Fraction Identified as B.p., ° C. (mm.) Distil- No. of
late (g.) Moles

1 p-Chloro- 56.5-59 (17) 38.2 0.30
toluene

2 p-Bromo- 65-70 (15) 106.5 0.63
toluene

Due to the hold up in a column of this type, and the small amount of
p-chlorobenzyl chloride probably produced, no fraction corresponding
to that of p-chlor0benzyl chloride was obtained.

The material boiling above 105° at 12 mm. from the reaction was
distilled from a Claisen.flask using a three-pronged type fraction cut-
ter and 125 ml. Erlenmeyer flasks to collect the following fractions.

Fraction Identified as B. P., ° 6. (mm.) Distil- No. of
late (g.) Moles

3 p-Bromobenzyl 106-121 (12) 108.5 0.53
chloride

4 p-Bromobenzyl 121-131 (12) 39.6 0.16
bromide

Upon recrystallizing fraction 3 from.95% alcohol, there was ob-
tained 94.5 g. (45.9% yield) of p-bromobenzyl chloride, m.p. 41-42.5°.

There'was obtained 27.8 g. of material melting at 54.5-56.5o upon
recrystallizing fraction 4 from.95% alcohol. This material evidently

was pabromobenzyl bromide contaminated with p-bromobenzyl chloride.

III. Chlorination of o-Bromotoluene.

 

A. Preliminary Investigation.
The material from several chlorination reactions was obtained from

Gyorgy and.distilled through the Fenske column previously described.

-42-

The following definite fractions were obtained:

Fraction Identified as B.p., ° 9. (mm.) nfio
1 e-Chlorotoluene 54.5-55 (20) 1.5263
2 o-B romotolu ene 68 .5 (19) 1 . 5560
3 o-Chlorobenzyl chloride 98.5-100 (17) 1.5621
4 o-Bromobenzyl chloride 112-114 (17) 1.5880
5 o-Bromob enzyl bromide 123-127 (17) --

1. Identification of o-Chlorotoluene.

The physical properties of fraction 1 were in agreement with those
given by Huntress (19) for o-chlorotoluene (b.p. 41° at 11 mm., 111230
1.52691).

An alkaline permanganate oxidation was carried out on fraction 1 ,
using the procedure described on page 34 for the oxidation of p-chloro-
toluene.

The product obtained from the oxidation of fraction 1 melted at
137-139° in a sealed capillary. When.admixed with an authentic sample

of o-chlorobenzoic acid, m.p. 137-139°, it showed no depression.

2. Identification of o-Bronmtoluene.
Since fraction 2 constituted such a large one and the boiling
point and refractive index checked closely with the values given by

Gyorgy (20), namely 7o-72° at 20 mm. and ngc

= 1.5550, for known o-bromo-
toluene, this material was considered as the o-bromotoluane recovered

from the chlorinations.

3. Identification of o-Chlorobenzyl Chloride.
Since o-chlorotoluene had been isolated and identified in the

chlorination and since the boiling point of fraction 3 agreed closely

-43-

with that given by Austin and Johnson (96-98° at. 14 mm.) (21) and
Bennett and Jones (94° at 15 mm.) (22), it was believed that fraction
3 was o-chlorobemzyl chloride.

Fraction 3 was identified as o-chlorobenzyl chloride by nitration
to 2-chloro-5-nitrobenzy1 chloride using essentially the procedure
described by Meisenheimer, Zimmermann, and v. Kummer (23).

Five grams of fraction 3 was placed in a 10 in. pyrex test tube
and heated to 50°. While mintaining the temperature between 30 and
35°, 10 m1. of fuming nitric acid was added dropwise from a separatory
funnel to the tube with shaking. After the acid had bem added, the
mixture was allowed to cool and then poured on cracked ice. By stir-
ring and scraping, a heavy 511an precipitate was obtained. This was
recrystallized twice from 95% alcohol to give light yellow needles,
m.p. 64-66".

Hitration of a known sample of o-chlorobensyl chloride by the
above procedure gave a product melting at 66°. A mixed melting point

gave a value of 65-660.

4. Identification of o-Bromobensyl Chloride.
Fraction 4 constituted the major fraction in the distillation.
The boiling point found was in agreement with that reported by Bennett

and Jones (IDS-106° at 12 me) (22) for o-bromobsazyl chloride.

5. Identification of o-Bromobenzyl Bromide.
The boiling point of fraction 5 us in agreement with that found
for known o-bromobenzyl bromide prepared as described on page 49. Also,

a capillary boiling point was taken and a value of 2153-234" at 743 -.

was obtained. A sample of known o-bromobenzyl bromide was found to
boil at 235-256° at 743 mm.

Fraction 5 was identified as o-bromobenzyl bromide by conversion
to the S-c-bromobenzylisothiourea picrate using a procedure described
by Levy and Campbell (24). '

One gram of powdered thiourea, 1 g. of fraction 5, 10 m1. of
ethanol, and a boiling chip were placed in a 10 in.pyrex test babe.

A finger condenser was placed in position and the mixture refluxed for
five minutes. At the and of this time, 1.0 g. of picric acid was in-
troduced and heating continued for an additional five minutes.

Upon cooling, the tube filled with a use of yellow needles. These
were filtered, recrystallized once from alcohol, and dried at room
temperature. The melting point of the product in a sealed capillary
was 221.5-2230. Levy and Campbell (24) reported 222° as the melting

point for S-c-bromobemzylisothiourea picrate.

B. Chlorination of o-Bromotoluene.

In order to determine the amounts of the products of the reaction,
a chlorination in daylight was carried out. The equipment was the
same as that described on page 41 for the chlorination of p-bromotoluene,

and the quantities of‘ reactants were as follows:

o-Bromotoluene -- 256.4 g. (1.5 moles)
Sulfuryl chloride -- 67.5 g. (0.5 mole)
Benzoyl peroxide -- 0.242 g. (0.001 mole)

Upon heating the reaction mixture to 60-65°, the characteristic

color change from light yellow to deep orange occurred. At 70°

evolution of gases began.but did not become vigorous until 950 was
reached. At this temperature the reaction was violent and external
cooling of the reaction‘vessel with an ice bath was necessary. When
it was noted that the reaction.was not proceeding spontaneously, the
mantle was adjusted and the mixture heated once more to 95°. .Again
the reaction started violently and external cooling was necessary.
However, this time the reaction proceeded smoothly for about twenty
minutes. The mixture was then heated to 120° for ten minutes and
after cooling transferred to a 500 m1. two-necked round-bottomed flask
fitted with a thermometer well and capillary tube. After pulling off
the corrosive gases with an aspirator, the distillation was carried

out through a Fenske colum.

Fraction Identified as B.p.,° 0. (mm.) Distil- No. of
late (g.) moles
1 o-Chlorotoluene 54-57.5 (20) 15.5 0.13
2 o-Bromotoluene 71-75 (21) 121.7 0.71
3 o-Chlorobenzyl 97.5-100 (17) 2.0 0.012
chloride
4 o-Bromobenzyl 110-114 (17) 32.9 0.16
chloride
5 o-Bromob enzyl 124-128 ( 17) 11.8 0.047
bromide

IV. Chlorination of mpBromotoluene.

For an investigation of the products formed in this reaction, the
material from several reactions was obtained from Gyorgy and vacuum
distilled through a.Fenske column. The following fractions were

collected:

-46-

Fraction Identified as B.p., o C. (mm.) Remarks

1 97-99.5 (17.5) n%?°6 . 1.5610

2 mpChlorobenzyl 99.5-101 (17.5) nfi9'6 = 1.5625
chloride

3 101-102 (17.5) n%9 = 1.5635

4 102-105 (17) né9°6 : 1.5661

5 105-116 (17)

6 mpBromobenzyl 116-118.5 (17) main fraction
chloride

7 118.5-129 (l7)

8 mpBromobenzyl 129-131.5 (17) large fraction,
bromide solidified.

Evidently all the mychlorotoluene and m-bromotolume had been stripped

from the reaction mixture by Gyorgy.

A. Identification of m-Chlorobenzyl Chloride.

Bennett and.Jonee (22) list a value of 104° at 17 mm. for the
boiling point of this compound. Although the refractive index of
fraction I agreed more closely to the value given by Robinson (n2!)0 3
1.5568) (25), fraction 2 was chosen for the identification. This was
necessary because fraction 1 was very small.

The identification of m-chlorobaizyl chloride was carried out by
the alkaline permanganate oxidation of fraction 2. The procedure used
was about the same as that described on page 34 for the oxidation of
p-chlorotoluene except that the solution was more alkaline; 16 drops of
6 N sodium hydroxide being used. The product melted at 156-157° while

that from the oxidation of known m-chlorotoluene melted at 153-1540.

A mixed melting point gave a value of 153.5-157°.

-47-

The material evidently must have been the m-chlorobenzyl chloride
and not the m—chlorobenzyl bromide which boils much higher (103--105o at

6 mm.) (26, 27).

B. Identification of m-Bromobenzyl Chloride.
Fraction 6 constituted the main fraction in the distillation.
This was considered as the m—bromobenzyl chloride since its boiling

point agreed with that given by Olivier (119° at 18 mm.) (28).

C. Identification of m-Bromobenzyl Bromide.

Fraction 8 which constituted a large fraction solidified as col-
lected. Known m-bromobemzyl bromide, prepared as described on page 50,
distilled at 125-127° at 12 mm. and also solidified when collected.

Fraction 8 was identified by its conversion to the S-m-bromoben-
zylisothiourea picrate by the method employed on page 45. The yellow
needles obtained were lighter in color than the corresponding ortho
isomer and melted at zoo-205°. Levy and Campbell (24) list 205° for

the melting point of S-m-bromobenzylisothiourea picrate.

V. The Preparation of the Bmmbenzyl Bromides.

 

The bromobenzyl bromides were prepared by a modification of the

method given by Coleman and Honeywell (29) and Brewster (30).

A. Preparation of p-Bromobenzyl Bromide.
Two-hundred-fifty-six and one half grams (1.5 moles) of p-bromo-
toluene was placed in a 1 1. three-necked, round-bottomed flask (ground

glass joints), which was fitted with an addition tube and bulb condenser,

.48...

a separatory funnel that reached below the surface of the p-bromo-
toluene, a thermometer, and an efficient mechanical stirrer.

The p-bromotoluene was heated slowly to 95° by means of a mntle.
At this tanperature, 51.7 ml. (79.9 g., 1.0 mole) of bromine (N.F.V.)
was added with stirring at a rate that just kept the solution void of
bromine color (about two hours). The temperature rose rapidly to 110°
and was maintained between 110-1200 during the addition. Throughout
the addition of bromine, the reaction mixture was illuminated with tw0
ISO-watt, unfrosted, tungsten lamps.

After all the bromine had been added, heating was discontinued and
the reaction mixture stirred for fifteen minutes. The contents of the
reaction flask was poured while still warm into a 250 ml. Claisen
flask, freed of gases with an aspirator and vacuum distilled using a
three-pronged fraction cutter and 125 m1. Erlmmeyer flask to collect
the fractions. The following fractions were obtained after the p-
bromotoluene had been removed.

IFraction B.p., °c. (mm.) Distillate Recrystallized M.p., °c.

(s-) (so)
1 125-130 (12) 157 124.5 61-62

The above fractions recrystallized from 95% alcohol as long colorless
needles, m.p. 61-62.5°, and amounted to 129.8 g. or’51.9%,'based on

the bromine used.

B. Preparation of o-Bromobenzyl Bromide.
The same equipment was used as for the preparation of p-bromoben-

zyl bromide. The following quantities of reactants were used:

-49-

o-Bromotoluene 299.3 g. (1.75 moles)

Bromine 51.7 m1., 158.4 g. (1.0 mole)
The o-bromotolusne was heated with stirring to 100° and the bromine
added slowly. As the reaction proceeded, the temperature rose quickly
to 135° and was maintained between 135-140° throughout the addition of
the bromine. This required about three and a half hours. After the
bromine had been added, heating was discontinued and stirring continued
for about ten minutes. The mixture was poured into a 500 m1. two-necked,
round-bottomed flask equipped with a thermometer well and a capillary
tube. After drawing off the gases with an aspirator, the material was

vacuum distilled through a Fenske column.

Fraction Product B.p., ° C. (m.) Distillate (g.)
l o-Bromotoluene 70-74 (17 ) 137
2 - 74-129 (17) 1.7
3 o-B romob enzyl 129-130 (16 .5) 198
bromide

The yield of o-bromobenzyl bromide, b.p. 129-130° at 16.5 mm., was 137
g. (79.2% based on bromine used or 95% based on the o-bromotoluene con-

sumed) .

C. Preparation of m-Bromobenzyl Bromide.

Two hundred six grams (1.20 moles) of m-bromotoluene, n30 -.- 1.5521,
was brominated with35.5 ml. (108.5 g., 0.685 mole) of bromine using
the procedure and equipment described above. The addition of bromine
was started as soon as the m-bromotoluene had reached 100°. The tempera-
ture rose quickly to 175° and remained betvmen 175-180° until all the

bromine had been added. This required an hour and a half. The reaction

-50-

mixture was distilled as previously described.

Fraction Product B.p., °c. (mm.) Distillate (g.)
l m-Bromotoluene 65-67 (12) 93.7
2 m-Bromob enzyl 12 5-127 (12 ) 128
bromide

The product, m-bromobenzyl bromide, was collected at 125-127° at 12 mm-
and weighed 128 g. (74.7% theory based on the bromine used, or 95.2%
on the m-bromotoluene consumed.) This product soon crystallized on

standing.

DISCUSSION

This investigation of the peroxide catalyzed chlorination of the
bromotoluenes with sulfuryl chloride has shown that the products ob-
tained are similar to those obtained by chlorination with molecular
chlorine. In addition to the recovered bromotoluenes and the expected
bromobenzyl chlorides as many as three other products were obtained
from each of the bromotoluenes. These are shown in Table I.

.It is evident from the products identified in the chlorination
that nuclear bromine replacement by chlorine takes place to a consid-
verable extent. This phenomenon is indeed strange when one considers
the work of Kharasch and Brown (1). By reacting 3.0 moles of n-propyl
bromide and 0.75 mole of sulfuryl chloride and using 0.001 mole of
benzoyl peroxide as a catalyst, they obtained a 50% yield of 1-bromo-2-
chloropropane and a 30% yield of 1-bromo-3-chloropropane. No n-propyl
chloride was isolated.

The recovery of relatively large ammmts of the chlorotoluenes
and very small amounts of the chlorobenzyl chlorides my be explained
by one or both of the following: (1) The initial concentration of the
chlorotoluene is very 8111111 and is increased during the course of the
reaction. Hence the amount of chlorotoluene present to be chlorinated
at the start of the reaction is very small and the chlorination proceeds
only as the concentration of chlorotoluene increases. (2) The reaction

betwoen free radicals of chlorine and the

.-CH2-C1 + c1- _.. G 65201 + Br-
Br Cl

TABLE I

MINOR PRODUCTS FROM THE CHLORINATION OF THE BROMOTOLUENES

 

 

 

Compound Products Method of
Chlorinated Identified Identification
o-Bromotoluene o-Chlorotoluene Oxidation of o-chlorcbenzoic
acid.
o-Chlorobenzyl Nitration to 2-chloro-5-
chloride nitro-benzyl chloride.
o-Bromobenzyl Conversion to S-o-bromo-
bromide bemzylisothiourea picrate.
m-Bromotoluene m-Chlorobenzyl Oxidation to m-chlorobenzoic
chloride acid. '
m-Bromobenzyl Conversion to S-m-bromo-
bromide benzylisothiourea picrate.
p-Bromotoluene p-Chlorotoluene Oxidation to p-chloro-
benzoic acid.
p-Chlorobenzyl Formation of the Grignard
chloride reagent, carbonation, and hy-
drolysis to p-chlorophenyl-
acatic geide
p-Bromobenzyl Analysis and mixed m.p. with
bromide a.known sample.

 

bromobenzyl chloride to yield chlorobenzyl chloride and free radicals
of bromine does not occur to any appreciable extent.

Bromination of the side chain also occurs during this chlorination
reaction. The bromine atom, after being replaced, is quite. reactive
and enters the side chain on it to form the bromobenzyl bromides, which
were isolated from the chlorination of each of the bromotoluenes. No
chlorobenzyl bromides were isolated. The bromobenzyl bromides are evi-
dently the high boiling products thought by Gyorgy to be the bromobenzal
chlorides.

Little or no effect emanated in the reaction when the chlorination
of p-bromotoluene was carried out in the dark or in the presence of a
solvent such as carbon tetrachloride. It is interesting to note, how-
ever, that the initiation temperature was higher (100° as compared to
93°) when the chlorination of p—bromo-toluene was performed in the dark.

In addition to the eleven possible equations suggested by Kharasch
and Brown (1) (see page 28) for explaining how the chlorination re-
action using sulfuryl chloride might proceed, the renewing four equa-

tions should be added for the bromotolumes:

c1 - + .433 ——o. 0 CH3 + Br-

Br Cl (12)
Br- «I .633 -—» .-CH2Br + H-

Br Br (13)

Br- 'P Br- ——-> Bra (14)

H- Q Br- —-> HBr (15)

Equations (14) and (15) represent chain-breaking or chain terminating
reactions. Although no evidence was obtained in favor of equation (15),
equation (14) probably does occur. The evidence for this was the
lchange of the reaction mixture from a light yellow to a deep orange
color as the temperature was raised and also the red-colored liquid
which flooded the condenser at the height of the chlorination reaction.
This method of chlorination appears to be quite useful in the
preparation of the chlorobenzyl chlorides (25). However, in the chlor-
ination of the bromotoluenes the yields are reduced considerably by
the side reactions, and the products formed are difficult to separate.
The bromobenzyl bromides have been prepared in.good yieldsfrom
the bromotoluenes by bromination in light from the unfrosted tungsten
lemme at temperatures near the boiling point. These bromobenzyl bro-
mides were useful in identifying like products which were formed in

the chlorination reaction.

-55-

2.

3.

4.

SUIMARY

The peroxide catalyzed chlorination of the bromotoluenes with

sulfuryl chloride has been investigated.

Nuclear bromine replacement by chlorine has been found to occur.
The bromine atom after being replaced enters the side chain of the

b romot olu enes .

In addition to the bromobenzyl chlorides, chlorotoluenes, chloro-
benzyl chlorides and bromobenzyl bromides have been identified as

products of the chlorination reaction.

The preparation of the bromobenzyl bromides in good yields is

described.

-56-

LITERATURE CITED

1. M. S. Kharasch and H. C. Brown, J. Am. Chem. Soc., 61, 2144 (1939).
2. H. Gyorgy, Ph. D. Thesis, Michigan State College, 1950.

3. A. Eibner, Ber., gg, 1230 (1903).

4. 0. Srpek, anatsh., 13, 431 (1090).

5. J. Boeseken, Rec. trav. chim.,'§§, 99 (1904).

6. W. A. Jacobs and M. Heidelberger, J. Biol. Chem., 22, 665 (1915).
7. H. Berger, J. prakt. Chem., Egg, 346 (1932). .

8. S. C. J. Olivier, Rec. trav. chhm., fig, 296 (1926).

9. F. Asinger, Mbnatsh., g5, 153 (1934).

10. E. H. Huntress, "Organic Chlorine Compounds," John'Wiley and Sons,
Inc., New'York, N. Y., 1948, p. 1139.

11. N. D. Cheronis and J. B. Entriken, "Semimicro Qualitative Organic
Analysis," Thomas Y. Crowell 00., New'York, N. Y., 1947, p.
175.

12. L. A. Bigelow’in “Organic Syntheses,” 2nd Ed., Coll. Vol. I, John
‘Wiley and Sons, Inc., New'York, N. Y., 1941, p. 13?.

13. Reference 2, p. 42.

14. Reference 10, p. 44.

15. Reference 11, p. 192.

16. G. Errera, Gazz. chim. ita1., 16, 239 (1898).

17. H. Stephen, W. F. Short and G. Cladding, J. Chem. Soc., 117, 510
(1920).

18. Reference 2, P0 420
19. ‘Reference 10, p. 1127.
20. Reference 2, p. 43.

21. P. R. AuStin and Jo Re JOhnson, Jo AID. Chemo 8°C., a, 657 (1932).

-57-

22.

23.

24.
25.
26.
27.
28.

29.

30.

G. M. Bennett and B. Jones, J. Chem. Soc., 1818 (1935).

J. v. Meisenheimer, P. Zinmermann, and U. v. Kummer, Ann., 446,
225-226 (1926).

W. J. Levy and N. Campbell, J. Chem. Soc., 1442 (1939).

K. Robinson, Ph. D. Thesis, Michigan State College, 1950.

Reference 10, p. 242.

s. s. Jenkins, J. Am. Chem. Soc., fig, 2898-2899 (1933).

s. 0. J. Olivier, Rec. trav. ohim., 33, 646 (1922).

G. H. Coleman and G. E. Honeywell in "Organic Syntheses," 2nd
Ed., Coll. Vol. II, John Wiley and Sons, Inc., New York,
N. Y., 1941, p. 443.

B. F. Brmter, Jo A111. Chem. 800., '29-, 406 (1918).

 

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